Gain of 1q Is a Potential Univariate Negative Prognostic Marker for Survival in Medulloblastoma

Lo, Ken C.; Ma, Changxing; Bundy, Brian N.; Pomeroy, Scott L.; Eberhart, Charles G.; Cowell, John K.

doi:10.1158/1078-0432.ccr-07-1420

Cited by 32 publications

(19 citation statements)

References 30 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Besides, our findings could also contribute to understand the biology of other neoplasms in which 1qG has been related to an adverse clinical outcome (Hing et al, 2001;Kjellman et al, 2001;Lo et al, 2007;Pezzolo et al, 2009;Balcarkova et al, 2009), as the mechanisms involved could be similar to those described here.…”

Section: Discussionsupporting

confidence: 64%

1q gain and CDT2 overexpression underlie an aggressive and highly proliferative form of Ewing sarcoma

et al. 2011

View full text Add to dashboard Cite

Despite extensive characterization of the role of the EWS-ETS fusions, little is known about secondary genetic alterations and their clinical contribution to Ewing sarcoma (ES). It has been demonstrated that the molecular structure of EWS-ETS lacks prognostic value. Moreover, CDKN2A deletion and TP53 mutation, despite carrying a poor prognosis, are infrequent. In this scenario identifying secondary genetic alterations with a significant prevalence could contribute to understand the molecular mechanisms underlying the most aggressive forms of ES. We screened a 67 ES tumor set for copy number alterations by array comparative genomic hybridization. 1q gain (1qG), detected in 31% of tumor samples, was found markedly associated with relapse and poor overall and disease-free survival and demonstrated a prognostic value independent of classical clinical parameters. Reanalysis of an expression dataset belonging to an independent tumor set (n ¼ 37) not only validated this finding but also led us to identify a transcriptomic profile of severe cell cycle deregulation in 1qG ES tumors. Consistently, a higher proliferation rate was detected in this tumor subset by Ki-67 immunohistochemistry. CDT2, a 1q-located candidate gene encoding a protein involved in ubiquitin ligase activity and significantly overexpressed in 1qG ES tumors, was validated in vitro and in vivo proving its major contribution to this molecular and clinical phenotype. This integrative genomic study of 105 ES tumors in overall renders the potential value of 1qG and CDT2 overexpression as prognostic biomarkers and also affords a rationale for the application of already available new therapeutic compounds selectively targeting the protein-ubiquitin machinery.

show abstract

Section: Discussionsupporting

confidence: 64%

1q gain and CDT2 overexpression underlie an aggressive and highly proliferative form of Ewing sarcoma

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Gain of chromosome 1q is a negative prognostic marker for survival also in medulloblastoma [57], but so far no correlation to the expression of Mcl-1 has been reported. Survivin is encoded by a single-copy gene located on human chromosome 17q25, a region that is frequently gained in unfavourable medulloblastoma and highrisk neuroblastoma [58][59][60].…”

Section: Deregulation Of the Intrinsic Apoptotic Pathwaymentioning

confidence: 97%

Embryonal neural tumours and cell death

et al. 2009

View full text Add to dashboard Cite

Medulloblastoma and neuroblastoma are malignant embryonal childhood tumours of the central and peripheral nervous systems, respectively, which often show poor clinical prognosis due to resistance to current chemotherapy. Both these tumours have deficient apoptotic machineries adopted from their respective progenitor cells. This review focuses on the specific background for tumour development, and highlights biological pathways that present potential targets for novel therapeutic approaches.

show abstract

“…In otherwise standard-risk medulloblastoma patients stratified by age >3 years and without metastatic disease, gain of 1q was significantly associated with poor survival (Lo et al, 2007a). An enzyme, hMOF, involved in histone acetylation, a process that is important for global regulation of gene transcription, cell proliferation, and response to DNA damage was shown to be downregulated in 40% (72 of 180) of medulloblastomas.…”

Section: Pediatric Astrocytomas (Gliomas)mentioning

confidence: 99%

Treatment of pediatric brain tumors

Karajannis

Allen

Newcomb

2008

Journal Cellular Physiology

View full text Add to dashboard Cite

Over the past decades considerable advances have been made in neurosurgery, radiotherapy and chemotherapy resulting in improved survival and cure rates for children with brain tumors. Here we review four of the most common subtypes of pediatric brain tumors, low-grade and high-grade astrocytomas, medulloblastomas and ependymomas, highlighting their molecular features regarding their tumor biology and promising potential therapeutic targets that may hold promise for finding new “molecularly targeted” drugs. Importantly, appropriate clinical trial design will play a critical role in the evaluation of new and novel treatment approaches for pediatric brain tumors.

show abstract

Gain of 1q Is a Potential Univariate Negative Prognostic Marker for Survival in Medulloblastoma

Abstract: Purpose: Tumor risk stratification during diagnosis is paramount for children with medulloblasto-

Cited by 32 publications

References 30 publications

1q gain and CDT2 overexpression underlie an aggressive and highly proliferative form of Ewing sarcoma

1q gain and CDT2 overexpression underlie an aggressive and highly proliferative form of Ewing sarcoma

Embryonal neural tumours and cell death

Treatment of pediatric brain tumors

Contact Info

Product

Resources

About